1. Field of the Invention
This invention relates to 4,4'-[9H-fluoren-9-ylidenebis(methylene)]bispyrimidines, pharmaceutical compositions containing them and methods of using them to treat neurological disorders in mammals.
2. State of the Art
Alzheimer's Disease (AD) and Senile Dementia (SD) are neurological disorders generally characterized by a reduction in cortical cholinergic activity. Neurological disorders may be characterized by altered neurotransmitter function and concomitant cognitive impairment in diseases such as, but not limited to, Alzheimer's Disease, Parkinson's Disease, Pick's Disease, Huntington's Disease, and Age Associated Memory Impairment. This had led to a focus on the basal forebrain cholinergic system as the major source of neurochemical and neuroanatomical substrates mediating age-related memory loss. However, it is very unlikely, given the complexity of the brain, that any single neurotransmitter would selectively and exclusively be involved in a neurological disorder so pervasive as dementia or age-related memory impairment. A growing literature has described multiple neurotransmitter, neuroanatomical and behavioral changes in dementia from varying etiologies It is, therefore, possible and likely that age-related memory deficits and cognitive impairment resulting from AD or SD involve concurrent changes in several neurotransmitter systems and neurotransmitters replacement therapy should involve multiple systems in the brain.
3. Information Disclosure
U.S. Pat. No. 4,760,083, issued July 26, 1988, and coassigned application Ser. No. 07/234,382, filed Aug. 23, 1988, (EP-A-311,010, Apr. 12, 1989), describe many compounds useful in the treatment of neurological disorders such as Alzheimer's Disease and Senile Dementia. In EP-A-311,010, certain 4,4'-[9H-fluoren-9-ylidenebis(methylene)]bispyridyl compounds are specifically disclosed as being useful in the treatment of neurological disorders. While the compound of the present invention is within the broad scope of Ser. No. 07/234,382, there is no suggestion that this compound has an unexpectedly good dosage profile as measured by hypoxia induced cognition impairment and a good safety margin.